International journal of molecular sciences, 2021-12, Vol.23 (1), p.73
2021
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- Autor(en) / Beteiligte
- Titel
- The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes
- Ist Teil von
- International journal of molecular sciences, 2021-12, Vol.23 (1), p.73
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in , , and gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients' poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms23010073Titel-ID: cdi_doaj_primary_oai_doaj_org_article_77ee0bd6371147ae89d6f2ac8ee5c1f2
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Animals, Apoptosis, Biomarkers, Biomarkers, Tumor - genetics, Breast cancer, Cancer therapies, Carbamoyl-Phosphate Synthase (Ammonia) - genetics, Carcinoma, Ovarian Epithelial - drug therapy, Carcinoma, Ovarian Epithelial - genetics, Cell Line, Tumor, Cell Survival - drug effects, Cell Survival - genetics, Chemotherapy, Clinical trials, CPS1, Down-Regulation - drug effects, Down-Regulation - genetics, Drug development, Drug Resistance, Neoplasm - genetics, Female, Gene expression, Genes, Humans, LIM Domain Proteins - genetics, Medical prognosis, Mice, Mice, Nude, Middle Aged, multidrug resistance, Multidrug Resistance-Associated Proteins - genetics, Ovarian cancer, Ovarian carcinoma, Ovarian Neoplasms - drug therapy, Ovarian Neoplasms - genetics, Paclitaxel, Paclitaxel - therapeutic use, Patients, Protein expression, Proteins, Signal transduction, Solid tumors, Stony Brook taxanes, Taxanes, Taxoids - therapeutic use, Therapeutic targets, Transcription Factors - genetics, TRIP6, Tumors, Xenografts, Xenotransplantation